Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 15 (2013) / Chapter Skim
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5 Lewisite Acute Exposure Guideline Levels
5 Lewisite Acute Exposure Guideline Levels
Pages 130-165
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From page 130... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels.
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Although the AEGL values represent threshold concentrations for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL. SUMMARY Because lewisite compounds were developed as chemical warfare agents, military literature is a major source of relevant toxicity data.
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Interspecies and intraspecies uncertainty factors of 3 each were applied. The interspecies uncertainty factor of 3 is supported by data suggesting little species variability with regard to lethality from inhalation exposure to lewisite; C × T values are relatively constant across species, except for the guinea pig, and the interspecies uncertainty factor of 3 encompasses the two- to three-fold difference in sensitivity between guinea pigs and rats, mice, rabbits, dogs, and goats.
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Exposure to lewisite causes almost immediate irritation and burning sensation of the eyes, skin, upper respiratory tract, and lungs. Death may result from direct pulmonary damage or circulatory failure from fluid loss and arrhythmia.
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. Therefore, AEGL values were derived for "lewisite" rather than for the individual lewisite compounds, and are considered protective for L-1, L-2, and L3.
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organic solvents USACHHPM 1996 Lewisite-3 (L-3) Insoluble in water; soluble in most USACHHPM 1996 organic solvents Insoluble in water; soluble in most organic solvents Vapor pressure Lewisite-1 (L or L-1)
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. To select "men of average resistance" for the study, pin-point drops of 0.1 or 2% solutions of liquid lewisite in alcohol were applied to the forearms of 52 male volunteers at Edgewood Arsenal.
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2.3. Developmental and Reproductive Effects Human developmental and reproductive toxicity data concerning lewisite were not found.
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Information suggesting an increased cancer incidence in workers from a Japanese poison gas factory is confounded because workers were exposed to several chemicals. Selected data on humans exposed to lewisite by inhalation are summarized in Table 5-5, and selected data on human exposed to liquid lewisite are presented in Table 5-6.
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to product solution (waste stream) from the chemical neutralization of Chemical Agent Identification Sets (CAIS)
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Lewisite concentrations in the exposure chamber were determined analytically from samples aspirated from the chamber during exposures. Clinical signs in dogs exposed for 7.5 or 15 min included detection of lewisite within 30 seconds, as evidenced by continual eye blinking, followed by excessive nasal secretion, lacrimation, and sneezing (Armstrong 1923)
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TABLE 5-7 Lethality Data from a Study of Dogs Exposed to Lewisite-1 Concentration LC50 Exposure Duration (mg/m3) Mortality (mg/m3)
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Rats No treatment-related deaths occurred in rats exposed a CAIS waste stream (containing chloroform [vehicle] , t-butanol [vehicle]
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At 0.6 mg/kg (highest dose in the teratology study) , effects included 86% maternal mortality, decreased maternal body weight gain, an increased incidence of fetal stunting, and a tendency toward decreased fetal body weight (Hackett et al.
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Animal data are limited but suggest that lewisite is highly irritating and corrosive, causing dermal and ocular lesions by contact with liquid or vapor. Inhalation LC50 values were identified in several species, and the weight of evidence suggests limited interspecies variability (C × T is relatively constant across species)
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Mechanism of Toxicity Dermal or intravenous exposure to lewisite leads to local skin edema and pulmonary edema due to increased capillary permeability. There is no evidence of edema or capillary permeability in any other part of the body.
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Toxicologic data on arsenic trichloride, L-2 and L-3, co-products concurrently formed with L-1, are limited. However, effects are similar qualitatively to those of L-1 (corrosiveness, damage to skin, eyes, and mucous membranes)
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Species Variability The selected animal mortality data presented in Table 5-8 show that the concentration-time products from LC50 data sets are relatively constant across species, except for the two guinea pig data points. This suggests that there is relatively little species variability with respect to lethal response to lewisite inhalation exposure.
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DATA ANA ALYSIS FOR R AEGL-2 6.1. 6 Human Da ata Relevant tto AEGL-2 No N human data were availablee for establishinng AEGL-2 vallues for lewisitee.
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DATA ANALYSIS FOR AEGL-3 7.1. Human Data Relevant to AEGL-3 No human data with concentration and duration parameters consistent with the definition of AEGL-3 were available.
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The interspecies uncertainty factor of 3 is supported by data that suggest little species variability with regard to lethality from inhalation exposure to lewisite; C × T values are relatively constant across species, except for the guinea pig, and the interspecies uncertainty factor of 3 encompasses the two- to three-fold difference in sensitivity between guinea pigs and rats, mice, rabbits, dogs, and goats (see Table 5-8 for summary of supporting data)
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9. REFERENCES Because lewisite compounds were developed as chemical warfare agents, military literature is a major source of relevant toxicity data.
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1944. Technical Command Chemical Warfare Center, Edgewood Arsenal, MD.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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1992. Toxicodynamics of organoarsenical chemical warfare agents.
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Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents. Washington, DC: National Academy Press.
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ADB954935. Edgewood Arsenal, Aberdeen Proving Ground, MD.
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and have comparatively low volatilities. Because of these chemical characteristics, AEGL-3 values for L-1 were adopted as AEGL-3 values for the mixture of L-1, L-2, and L-3.
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ADB954935. Edgewood Arsenal, Aberdeen Proving Ground, MD.
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Intraspecies: 3, steep concentration-response curve with regard to lethality implies limited intraspecies variation. In studies with mice, the 10-min LC50 was 200 mg/m3 and the 10-min LC100 was 240 mg/m3.
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160 Acute Exposure Guideline Levels APPENDIX C CALCULATION OF LC01 VALUE FOR DOGS Data source: Armstrong (1923) Filename: ten Berge Spreadsheet Data for Log Probit Model Date: 15 October 2010 Time: 09:03:51 Sequence No.
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concentration mg/m3 = 2.064E+01 for response of 1% Estimation of concentration mg/m3 at response of 1% Minutes = 60 Point estimate concentration mg/m3 = 7.400E+00 for response of 1% Lower limit (95% CL) concentration mg/m3 = 3.237E+00 for response of 1% Upper limit (95% CL)
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concentration mg/m3 = 5.838E+00 for response of 1% Estimation of concentration mg/m3 at response of 1% Minutes = 240 Point estimate concentration mg/m3 = 2.058E+00 for response of 1% Lower limit (95% CL) concentration mg/m3 = 8.675E-01 for response of 1% Upper limit (95% CL)
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From page 163... ...
Lewisitte 1163 AP PPENDIX D CATEGORY C PLOT P FOR L LEWISITE FIGUR RE D-1 Category y plot of animaal and human tooxicity data andd AEGL values for lewisitee.
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164 TABLE D-1 Data Used in the Category Plot for Lewisite Source Species Sex No. of Exposures mg/m3 Minutes Category Comments AEGL-1 NR 10 AEGL AEGL-1 NR 30 AEGL AEGL-1 NR 60 AEGL AEGL-1 NR 240 AEGL AEGL-1 NR 480 AEGL AEGL-2 1.3 10 AEGL AEGL-2 0.47 30 AEGL AEGL-2 0.25 60 AEGL AEGL-2 0.070 240 AEGL AEGL-2 0.037 480 AEGL AEGL-3 3.9 10 AEGL AEGL-3 1.4 30 AEGL AEGL-3 0.74 60 AEGL AEGL-3 0.21 240 AEGL AEGL-3 0.11 480 AEGL Franke 1968 Human 1 10 30 2 Severe intoxication, incapacitation Silver and McGrath 1943 Mouse Male 1 240 10 3 Mortality (10/10)
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Gates et al. 1946 Guinea pig 1 8 60 SL LC50 Gates et al.
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